The no observable adverse effect level for male mice was 2.5 mg of pentamidine isethionate/kg/day. Dosages of 5 and 10 mg of pentamidine isethionate/kg/day caused some reduced body weight gains in male mice. Transient hypoactivity was detected in male and female (b) mice in the 10 mg/kg/day dose group. The NOAEL for general toxicity for female mice was 5 mg/kg/day. Dosages of 10 mg of pentamidine isethionate/kg/day and higher caused mortality, decreased body weights, and clinical observations of toxicity ranging from hypoactivity to seizures. The NOAEL for developmental toxicity was 10 mg of pentamidine isethionate/kg/day. Dosages of 20 mg of pentamidine isethionate/kg/day produced decreased fetal body weights.
The toxicity of pentamidine isethionate was assessed in Swiss male and female mice by intravenous administration at dose levels ranging from 2 .5 to 40 mg/kg/day. Male mice (10/group) were dosed with 2.5, 5, and 10 mg of the test article/kg/day on study days 5 to 24 and were sacrificed on day 25. Prior to dosing (study days 0 to 4) the male mice were cohabited with female mice (20/group), designated as females. The sperm-positive female mice were dosed at 2.5, 5, and 10 mg of pentamidine isethionate/kg/day on days 6 through 15 of gestation and were sacrificed on scheduled day 4 of lactation. A second group of female mice (20/group), designated as females (a), was dosed with 5, 10, 20, and 40 mg of pentamidine isethionate/kg/day beginning on study day 0 and throughout mating on study days 9 to 13 until the day prior to scheduled sacrifice on scheduled Day 18 of gestation. All female mice treated with 40 mg of pentamidine isethionate/kg/day died prior to mating. Adult mice were evaluated for clinical signs, body weights, and clinical pathology parameters. Male mice were subjected to a sperm function evaluation. Offspring from each group were evaluated for viability, external anomalies, and weight.